Sarcoid-like reactions in patients receiving modern melanoma treatment

Abstract

The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today’s standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features. We carried out a single-center observational study in patients with stage IIB–IV melanoma treated with BRAF/MEK inhibitors and immune checkpoint inhibitors. A description of the sarcoidosis-related manifestations was provided from patients’ records. We observated eight cases of SLRs in a cohort of 200 patients. The clinical courses were characterized by a variety of symptoms, accompanied by cutaneous signs and extracutaneous manifestations such as bilateral, hilar lymphadenopathy. We identified a histologically granulomatous inflammation involving the skin, the lungs, and the lymph nodes. Two patients presented with cutaneous lesions only, and three patients had lung involvement only. Three patients achieved complete and partial response of the melanoma disease, and three patients had stable disease. Disease progression was documented in two patients. The reported immune-related adverse events were mild to severe and in most of the cases were continued without any treatment cessation. SLRs appear during treatment with both kinase and immune checkpoint inhibitors. Awareness of these can avoid misdiagnosis of disease progression and unnecessary treatment changes.

Cutaneous Malignant Melanoma Metastasis to the Pseudophakic Lens Capsule with Associated Granulomatous Intraocular Inflammation

“…Phacolysis can induce a granulomatous response; however, the patient had quiet pseudophakia for many years preceding presentation, rendering this very unlikely. Immunotherapeutic agents used in the treatment of malignant melanoma are increasingly associated with intraocular inflammation [11]; however, vitreous biopsy in our case preceded any use of immunotherapy by the patient. Finally, the patient could have an associated granulomatous pathology, such as sarcoidosis, Ocul Oncol Pathol 2020;6:339-343 DOI: 10.1159/000507052 which has been described in the literature in melanoma patients [12,13].…”

Rapidly Evolving Extensive Fluorodeoxyglucose-Positive Soft-Tissue Activity During Nivolumab Therapy

“…Erythema nodosum is also reported to be the most common drug-induced panniculitis. 7 In the setting of immune checkpoint inhibitors used for cellmediated immunity, few reports in the literature have described a sarcoidlike granulomatous panniculitis. [7][8][9] The typical histological pattern includes partly granulomatous reactions with mixed septal and lobular inflammatory infiltrate with lymphocytes and epithelioid histiocytes.…”

Nicht‐infektiöse granulomatöse Dermatosen

“…Hinsichtlich moderner Melanomtherapeutika zeigt die neuere Literatur das Auftreten granulomatöser Dermatosen oder granulomatöser Erkrankungen mit kutaner Beteiligung sowohl unter BRAF‐MEK‐Inhibitoren als auch unter Immuncheckpoint‐Inhibitoren . Es wurden dabei unter anderem ein dem Granuloma anulare ähnliches Bild und das Bild einer interstitiellen granulomatösen Dermatitis beschrieben, wobei unterschiedliche histologische Bilder bei einem Patienten vorliegen können (Lee et al., 2016) Interessanterweise wurde gezeigt, dass das histologische Bild einer granulomatösen Dermatose beispielsweise unter der Therapie mit einem BRAF‐Inhibitor bereits in subklinischen Läsionen wie dem Gewebematerial einer solaren Lentigo detektierbar war .…”